tbuckley/cabot-search huggingface dataset:
Abstract 15025: Bone Marrow Cells Transdifferentiate Into Heterogenous Populations of Endothelial Cells in the Heart
Authors: Parisa Shabani, Lindsay Shockling, Molly Enrick, Ammar Alghadeer, Chris Kolz, Vahagn A Ohanyan, Feng Dong, Ping Zhang, Xin Shi, Liya Yin, William M Chilian
Journal: Circulation (2022)

Introduction: A substantial number of studies in animal as well as human have shown contribution of bone marrow (BM) derived cells to postnatal angiogenesis in physiological and pathological conditions. Despite this information, questions remain regarding whether bone marrow-derived cells can become endothelial cells and engraft in blood vessels. Methods: To address this question, we generated chimeric rats containing BM from transgenic rat with the ubiquitin promoter driving GFP (GFP + BM) that was transplanted into a wild-type irradiated recipient. Chimeric rats were subjected to repetitive ischemia (RI, LAD occlusion) over a period of 17 days using a model in which the LAD is subjected to episodic ischemia to induce angiogenesis and collateral growth. Results: Measurements of myocardial blood flow (MBF) in the collateral-dependent region revealed a 3-fold increase in the ratio of collateral-dependent to normal zone MBF after 17 days. This increase in flow is due to collateral growth and angiogenesis in the ischemic region. Fluorescence microscopy in conjunction with immunostaining for rat endothelial cell antigen-1 showed the BM derived endothelial cells integrated into coronary blood vessels. We performed single cell RNAseq after sorting GFP + /propidium iodide - cells from hearts (enzymatic digestion) and bone marrow of control and RI rats. After quality filtering we had a total of 24103 cells. Clustering the cells identified 28 clusters. we annotated endothelial cell clusters based on the expression of endothelial cell markers. We had comparable proportion of endothelial cell populations in control and RI groups. Using canonical markers of different endothelial cell subtypes, we characterized arterial, venous, capillary, and lymphatic subpopulations within endothelial cell cluster. The endothelial cell population in the RI group had more angiogenic profile with higher expression of angiogenesis markers and vessel development pathways in gene ontology analysis. Conclusions: Taken together, our data suggest that BM cells can differentiate into endothelial cells in hearts, representing a heterogenous population of endothelial cells and contributing to vascular growth.
Abstract 15624: The Impact of One versus Three Readings on Pediatric Hypertension Diagnosis is Mediated via Diastolic Blood Pressure
Authors: Sandeep Riar, Brian Lee
Journal: Circulation (2022)

Introduction: Blood pressure (BP) is affected by many factors. In pre-teen children, the hypertension (HTN) threshold is about 4 mmHg higher for systolic and about 3 mmHg for diastolic BP. Single BP reading is the norm in real life clinical practice even as HTN guidelines and research use multiple BP readings. There is limited data on the within-visit BP variability in children. The National Health and Nutrition Examination Survey (NHANES) is a population-based survey and 3 BP readings are obtained using a standardized protocol. We aimed to study the difference between single versus 3 BP readings using NHANES data. Methods: In the 2017-2018 NHANES, participants aged 8 years and older underwent BP measurement using 2 protocols. The auscultation protocol (AP) was administered by a physician using a mercury sphygmomanometer. The oscillometric protocol (OP) was administered by a health technician using an Omron HEM-907 XL device. We included participants 8 to 17 years old with 3 AP and 3 OP BP readings for comparison and excluded those with DBP of zero. Results: There were 1126 subjects who met inclusion criteria. The proportion of SBP readings with a difference of at least 5 mmHg between the initial and subsequent 2 BP readings was greater with OP but greater with AP for DBP (Table 2). Similar trend was noted with comparison of initial and mean of all 3 BP readings. Coefficient of variation was higher for DBP than SBP. The proportion of patients with hypertension range BP was significantly higher for DBP than for SBP (table 3). Conclusions: Diastolic BP shows more variability with multiple measurements. Hypertension range BP was noted more often with the initial DBP measurement than with 3 BP readings.
Abstract 206: Easily Created Prediction Model Using Deep Learning For Termination Of Resuscitation (tor) In Out Of Hospital Cardiac Arrest (ohca) Cases: The All-japan Utstein Registry Experience.
Authors: Kentaro Kajino, Marcus Ong, Mohamud R Daya, Atsunori Onoe, Yasuyuki Kuwagata
Journal: Circulation (2022)

Background: Correct identification of futile prehospital resuscitation in out-of-hospital cardiac arrest (OHCA) may reduce unnecessary transports. Reliable prediction variables are needed for 'termination of resuscitation' (TOR) rules in OHCA. However, making such prediction models requires a large number of samples and time-consuming statistical analysis. Deep learning (DL), a form of artificial intelligence (AI), is attractive for building such prediction models. We made a TOR prediction model using a DL software, Prediction One (Sony Network Communications Inc., Tokyo, Japan). The purpose of this study was to evaluate the efficacy of this predictive model using general purpose AI compared to the Universal TOR rule for out - of hospital cardiac arrest. Methods: A retrospective, population-based review of OHCA victims without prehospital ROSC from January 1, 2010 to December 31, 2017 in the All-Japan Utstein Registry. We divided half (2010-2014) as a training dataset and half (2015-2017) as an external validation dataset. Prediction one made the prediction model using the training dataset with internal cross-validation. We used both the created model and the Universal TOR rule to predict outcomes using the external validation set. Results: 989,929 OHCA cases, 18 years of age or older, were registered in the All-Japan Utstein Registry and 575,346 cases were of presumed cardiac origin. Of these, 354,356 cases were used as the training dataset and 220,990 cases were used as the external validation dataset. The model made by Prediction One using 11 variables had AUC of 0.969 and F value of 0.969, and its AUC for the validation cohort was 0.964 (95%CI 0.963-0.966) with 99.3% accuracy. The model made by Prediction One using three variables of universal TOR rule had AUC of 0.948 and F value 0.967, and its AUC for the validation cohort was 0.939 (95%CI 0.936-0.942) with 99.1% accuracy. Conclusions: The accuracy of prediction models using Prediction One was good. More research into the utility of using AI for TOR prediction is required.
Abstract 15443: Association Between Central Sleep Apnea and P2y12 Inhibitors in Patients With Coronary Heart Disease
Authors: William S Tzeng, Christian Klein, Robert Roth, Yeilim Cho, Rohit Munagala, William Healy, Jennifer Lobo, Sula Mazimba, Younghoon Kwon
Journal: Circulation (2022)

Introduction: Central sleep apnea (CSA) is common in patients with heart failure and is associated with a poor prognosis. A number of studies have linked the P2Y12 inhibitor, ticagrelor, with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA in this population. Methods: We reviewed consecutive patients with CHD data who underwent a clinically indicated polysomnography (PSG) test over a 5-year period from three academic sleep centers. We sampled patients who were on ticagrelor or clopidogrel during their PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription at time of PSG test were excluded. Age, left ventricle (LV) dysfunction (ejection fraction &lt;45%), and P2Y12 inhibitor use were included in a multivariate logistic regression. Results: A total of 141 patients (age 63.7 ± 11.4, 33% female) were included with 30 on ticagrelor and 111 on clopidogrel. 106 (75.2%) patients had undergone percutaneous coronary intervention for ACS. 33 (23.4%) patients had LV dysfunction. The mean apnea hypopnea index (AHI) was 29 (/hr). High CSA burden (central apnea index [CAI] ≥5/h) and strict CSA (AHI ≥5/h and CAI &gt;50% of AHI) were present in 16 (11.3%) and 5 (3.5%) patients, respectively. High CSA burden and strict CSA were more common in patients on ticagrelor than in those on clopidogrel (7 [23.3%] vs. 9 [8.1%] and 3 [10.0%] vs. 2 [1.8%]). In multivariable analysis ticagrelor use was associated with high CSA burden adjusting for LV dysfunction and age (OR 3.27, 95% CI 0.99-10.7, p=0.048). No variables were associated with strict CSA. Conclusions: Ticagrelor use was associated with high CSA burden in patients with coronary heart disease. Future studies should verify these results in a larger cohort and explore their clinical significance.
Abstract 242: Association Of The Nearest Static AED With Treatment And Outcome Of OHCA In Forsyth County, North Carolina
Authors: Jerishma Patel, Eric S Yow, Faraan Rahim, Sreekanth Yellanki, Hanul Choi, Denise Simmons, Konstantin Krychtiuk, Audrey L Blewer, Cynthia Green, Darrell Nelson, Tyson Clark, Patrick H Pun, Christopher Granger, Daniel B Mark, Monique A Starks
Journal: Circulation (2022)

Introduction: Over the last two decades, publicly accessible AEDs have become available in communities across the US, allowing bystanders to rapidly intervene during OHCA. The impact of static AEDs on rates of bystander AED application and OHCA outcomes is poorly understood. Methods: We created a static AED registry for Forsyth County, NC (mixed rural-urban county with population ~ 380,000 ) primarily through phone-based surveys of businesses. These data were linked to the Cardiac Arrest Registry to Enhance Survival and geocoded to calculate proximity between OHCA and nearest static AED. The AHA recommends that publicly accessible AEDs be placed to achieve bystander retrieval within 100 meters (m) of OHCA. Multivariable logistic regression modeling examined the relationship between AED proximity and survival to hospital discharge. Results: Included were 2078 patients &gt;18 years old with OHCA between 2013-2019 and 573 businesses with at least one AED. There were 219 (10.5%), 190 (9.1%), 1669 (80.3%) OHCAs with an AED within &lt;100m, 100-200m, and &gt;200m, respectively. OHCA incidence was highest where static AEDs were closest. Static AEDs within 100m of OHCA were primarily at residential facilities (41.1%), health care clinics (26.5%), churches (9.1%), and schools (6.8%). Among OHCAs with nearest AED &gt;200m, AEDs were primarily owned by schools (32.2%), healthcare facilities (15%), industrial facilities (10.6%), and churches (10.4%). Bystander CPR was highest for OHCAs in closest proximity to an AED (&lt;100m: 61.2%; 100-200m: 51.6%; &gt;200m: 39.5%, p&lt;0.001). Bystander AED application was highest where static AEDs were closest to OHCA (28.3%, 14.2%, and 3.8% at &lt;100m, 100-200m, and &gt;200m, respectively, p&lt;0.001). Among patients who were defibrillated, bystander defibrillation was 18.1%, 20%, and 3.9% (p&lt;0.001). There was no difference for survival to hospital discharge (&lt;100m: 15.1%; 100-200m: 15.3%; &gt;200m: 13.1%, p=0.54), even after adjustment (aOR 1.002, 95% CI 0.995-1.008 per 10m decrease). Conclusion: Only 10% of OHCAs in Forsyth County were within 100 meters of a static AED. Bystander CPR and AED application were highest where static AEDs were &lt;100m from OHCA. Despite this, there was no association between AED proximity and survival to hospital discharge.
Abstract 15367: Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women With Suspected Myocardial Ischemia: The Women’s Ischemia Syndrome Evaluation (WISE &amp; WISE-CVD) Projects
Authors: Nicole Virzi, David Krantz, Vera A Bittner, C. Noel Bairey Merz, Steven Reis, Eileen M Handberg, Carl Pepine, Thomas Rutledge
Journal: Circulation (2022)

Introduction: Ischemic Heart Disease (IHD) risk in women includes biomedical, behavioral, and psychosocial contributors. Among psychosocial contributors, recent studies suggest that depression, especially somatic symptoms of depression such as anhedonia and low energy, may play a disproportionate role in the development of both IHD risk factors and major adverse cardiovascular events (MACE). Methods: We examined relationships between cognitive/somatic symptoms of depression and metabolic syndrome (MetS) in two independent cohorts of women with suspected IHD. In the Women’s Ischemia Syndrome Evaluation (WISE, NCT00000554), we also examined depression and MetS as predictors of all-cause mortality and MACE over a median 9.3-year follow-up. The sample from WISE included 641 women with suspected ischemia with or without obstructive coronary artery disease (CAD). The WISE-Coronary Vascular Dysfunction (WISE-CVD, NCT00832702) consisted of 359 women with suspected ischemia and no obstructive CAD (INOCA). Somatic, cognitive, and total depressive symptoms were measured via the Beck Depression Inventory (BDI). MetS was assessed according to the AHA’s ATP-III criteria. Results: (See attached table) In both the WISE and WISE-CVD samples, somatic symptoms of depression were associated with MetS diagnosis and MetS severity, while cognitive symptoms were not. Within the WISE sample, using Cox Proportional Hazard Regression, both somatic symptoms and MetS diagnosis were significant predictors of all-cause mortality and MACE, while cognitive symptoms were not. Conclusions: In two independent samples of women undergoing coronary angiography for suspected myocardial ischemia, somatic symptoms of depression were uniquely associated with both MetS and all-cause mortality and MACE, and both somatic symptoms of depression and MetS independently predicted all-cause mortality and MACE.
Abstract 258: Age, Sex And Survival Of Ventricular Fibrillation Out-of-Hospital Cardiac Arrest: The Influence Of Electrocardiogram Waveform Measures
Authors: Betty Y Yang, Jason Coult, Jennifer E Blackwood, Heemun Kwok, Anjali Rajah, Ilan Goldenberg, Nona Sootedehnia, Peter J Kudenchuk, Thomas Rea
Journal: Circulation (2022)

Background: Studies of sex-based outcome in out-of-hospital cardiac arrest (OHCA) have produced mixed results that may depend on age. Menopause produces a range of effects that may influence resuscitation. We used quantitative measures of the presenting OHCA ventricular fibrillation (VF) waveform - a surrogate of the myocardium’s acute physiology - to assess whether outcome differences according to sex and age group may be mediated via a biologic mechanism. Methods: We conducted a retrospective cohort study of adults with non-traumatic VF-OHCA in a metropolitan Emergency Medical Services system between 2008-2020. We used multivariable logistic regression to assess the association of outcome (survival to hospital discharge, favorable neurological outcome (Cerebral Performance Category (CPC) 1 or 2), with sex and age group (&lt;55, &gt; 55 yrs). We then determined the proportion of the outcome difference mediated by the waveform measure by incorporating previously described quantitative VF waveform measures - an estimated probability of survival (P Survival ) and amplitude spectrum area (AMSA - into the model individually. Results: Of 1526 VF-OHCA patients, average age was 62 years, and 29% were female. Overall, younger women were more likely to survive than younger men (survival 67% vs 54%, p=0.02 with CPC 1-2 61% vs 51%, p=0.07), while older women and older men had similar worse outcomes. After adjusting for Utstein characteristics, women &lt;55 compared to men &lt;55 was associated with greater odds of survival to hospital discharge (OR 1.93, 95% CI 1.23-3.09, p=0.005) and CPC 1-2 survival (OR 1.72, 95% CI 1.10-2.71, p=0.02), whereas no associated sex-based differences in these outcomes were observed between the older groups. Each waveform measure mediated some of the beneficial association between sex and age group with survival: 47% for P Survival and 25% AMSA. Conclusions: Women &lt;55 years were more likely to survive to hospital discharge and with favorable neurological status compared to men &lt;55 years, a sex-associated outcome difference not observed in the older age group. The biologic mechanism represented by VF waveform measures mediated some (47% at most), though not all, of the outcome differences.
Abstract 15761: SMYD1 Regulates OPA1-Mediated Cristae Remodeling and Supercomplex Formation to Protect From Ischemic Injury
Authors: Marta Szulik, Steven Valdez, Maureen Walsh, Kathryn Davis, Ryan Bia, Emilee Horiuchi, Sean O'Very, Linda Nicolova, Hanin Sheikh, Samuel Hickenlooper, Magnus Creed, Mickey R Miller, Li Wang, June Garcia-Llano, Chris Tracy, Stavros G Drakos, Katsuhiko Funai, Dipayan Chaudhuri, Sihem Boudina, Sarah Franklin
Journal: Circulation (2022)

SMYD1 is a lysine methyltransferase, which has been shown to methylate lysine 4 on histone H3, an established mark of gene activation. SMYD1 is only expressed in skeletal and cardiac muscle and was originally shown to play a significant role in regulating cardiac development. In the adult myocardium, using inducible, cardiomyocyte-specific Smyd1 knockout mice, loss of SMYD1 leads to massive downregulation of mitochondrial bioenergetics and overt heart failure. However, the effects of SMYD1 gain-of-function in the heart and its molecular function in the cardiomyocyte in response to ischemic stress remains unknown. Here we demonstrate that SMYD1a, the mouse ortholog of human SMYD1, positively regulates cardiac energetics and protects the heart from ischemic injury. To delineate how SMYD1a controls energy efficiency and metabolism in the cardiomyocyte, we generated a novel mouse model capable of inducible cardiomyocyte-specific SMYD1a overexpression. When subjected to ischemic injury these transgenic mice display reduced infarct size and cardiomyocyte death concomitant with enhanced mitochondrial respiratory efficiency. In addition, our molecular analysis revealed that the cardiac tissue in these animals is protected from ischemic injury through SMYD1a’s synergistic regulation of two key mitochondrial pathways. First, through its histone methyltransferase activity, SMYD1a maintains metabolic homeostasis by preserving basal expression of PGC-1α and its downstream targets including electron transport chain subunits. Second, SMYD1a regulates expression of OPA1, a key regulator of cristae morphology which drives the formation of electron transport chain supercomplexes to enhance mitochondrial respiration and ATP production. This work highlights SMYD1a as the only known epigenetic regulator of cristae morphology and identifies a novel molecular pathway by which cardiomyocytes dynamically regulate energy efficiency to protect from ischemic injury.
Abstract 14920: Differences in Socioeconomic Factors in Patients Obtaining Coronary Calcium Score Computed Tomography in a Large Midwestern Healthcare Network
Authors: Andrew Chapel, Viviana Zlochiver, James Adefisoye, Kritika Garg, Alexander Reddy, Michael Peterson, Doreen Plautz, Jessica Kram, Steven Port, Patrycja Galazka
Journal: Circulation (2022)

Introduction: Coronary artery calcium score (CACS) is an important tool for identifying subclinical atherosclerosis and cardiovascular risk stratification. The 2018 ACC/AHA Cholesterol Guideline includes CACS as a decision aid in asymptomatic, intermediate-risk patients. In most US states, including Wisconsin, CACS is not covered by insurance with out-of-pocket costs ranging from $50-400. This study aimed to examine the socioeconomic factors of Wisconsin patients who obtained a CACS CT at Advocate Aurora Health (AAH). Methods: Using the 2018 American Community Survey data from the Census Bureau, we evaluated the socioeconomic characteristics of the areas in Wisconsin where patients who underwent CACS CT at AAH lived. These included race, ethnicity, median income, median age, average household size, household without vehicles, and completion of high school. We categorized the income as low (≤$35,000), medium (&gt;$35,000 - &lt;$100,000), and high (≥$100,000). Additionally, we compared self-referred versus physician-referred patient characteristics. Results: A total of 19,726 patients presented for CACS CT at AAH from 2019 through 2021. The median income for patient residential areas was $73,981. The median percentage of white race in these areas was 94.6%, while that of black race was only 0.3%. Additionally, median percentage of Hispanics was 2.9%. The median average household size was 2.5 people, median percentage of households who did not own a vehicle was 2.2%, and the median high school completion rate was 95.2%. When we stratified by income, most patients were from areas with medium income (75.2%), followed by high (17.3%), and only 7.5% were from low-income areas. When comparing self-referred versus physician-referred patients, self-referred were found to live in higher-income areas compared to physicians-referred (19.4% vs. 16.4%; p&lt;0.0001). Conclusion: Social and economic factors are well known to affect access to health care. Our study demonstrated that patients in Wisconsin who obtain out-of-pocket CACS CT live predominantly in medium and high-income areas. Patient access to preventive health care may be affected by the lack of insurance coverage.
Abstract 15187: Comparison of Resting and Hyperemic Coronary Physiological Indices to Evaluate Myocardial Bridging in Patients With Angina and No Obstructive Coronary Arteries
Authors: Vedant S Pargaonkar, Ingela Schnittger, Jennifer A Tremmel
Journal: Circulation (2022)

Introduction: A hemodynamically significant myocardial bridge (MB) is an important diagnosis in patients with angina and no obstructive coronary arteries (ANOCA). The most appropriate intracoronary functional assessment to distinguish an incidental vs. hemodynamically significant MB remains unclear. We compared the ability of several resting and hyperemic physiological indices to identify a hemodynamically significant MB. Methods: We prospectively studied 11 patients with ANOCA and an MB confirmed by intravascular ultrasound (IVUS). All patients had intracoronary functional testing at rest, including instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), and the ratio of distal coronary pressure (Pd)/aortic pressure (Pa). These measurements were repeated at hyperemia, including adenosine fractional flow reserve (FFR), dobutamine diastolic FFR (dFFR), iFR, and RFR. Resting iFR and RFR ≤ 0.89; resting Pd/Pa ≤ 0.91; hyperemic FFR, iFR, and RFR ≤ 0.8; and dFFR ≤ 0.76 were considered indicative of hemodynamic significance of an MB. Dobutamine dFFR was considered as reference standard. Results: At rest, iFR and RFR were significant in 6 and 7 patients respectively, while Pd/Pa was significant in 6. Adenosine FFR was significant in only 4 patients. With dobutamine, iFR and RFR were significant in 8 and 9 patients, respectively, and dFFR was significant in 9. Resting Pd/Pa and hyperemic iFR had a strong positive Spearman's rank correlation coefficient with dFFR (Figure). By kappa statistics, dobutamine iFR and RFR had almost perfect agreement with dobutamine dFFR. Conclusion: In patients with ANOCA who have an MB by IVUS, intracoronary physiology assessment is necessary to determine if the MB is hemodynamic significant. While adenosine FFR is an insufficient measure, diastolic indices such as dobutamine dFFR, iFR, or RFR may identify hemodynamic significance, although whether one diastolic index outperforms another requires further evaluation.